Evidence map›Paper›PMID 41443038›Full record

ArticleBiomaterials2026

Drug resistant cancer cells show increased nuclear mechanotransduction and mechanically targetable YAP-regulated vulnerability.

Miao Huang, Yinong Chen, Chenyu Liang, Om Prakash Narayan, Chase Stallings, Mu Yu, Conner Traugot, Lu Li, Keming Li, Quang Vo and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors.

Miao HuangDepartment of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32610, USA; UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA.
Yinong ChenDepartment of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32610, USA; UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, 32610, USA.
Chenyu LiangDepartment of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32610, USA; UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA.
Om Prakash NarayanCollege of Pharmacy, Division of Chemical Biology and Medicinal Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Chase StallingsDepartment of Biology, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, 32610, USA.
Mu YuUF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, 32610, USA.
Conner TraugotUF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA.
Lu LiUF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA.
Keming LiMechanobiology Institute, National University of Singapore, Singapore.
Quang VoDepartment of Biology, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, 32610, USA.
Heyang WangDepartment of Mechanical Engineering, Robert R. McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
Yu-Ting ChouDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Lauren CechDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Daniel ParraDepartment of Computer & Information Science & Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32610, USA.
Laura GarzonDepartment of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32610, USA.
Dylan ParsonsDepartment of Biology, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, 32610, USA.
Emma DiazDepartment of Applied Physiology & Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, FL, 32610, USA.
Cunyu ZhangThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518000, China; Research Institute of Smart Ageing, The Hong Kong Polytechnic University, 999077, Hong Kong, China; Department of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, China.
Cole MackeyDepartment of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA.
Hayley SussmanDepartment of Biomedical Engineering, School of Engineering & School of Medicine, University of Virginia, VA, 22904, USA.
Izabela ZmirskaJ. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, 32610, USA.
Michael ChungCollege of Pharmacy, Division of Chemical Biology and Medicinal Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
Chen ZhouDepartment of Medicinal Chemistry, University of Florida, Gainesville, FL, 32610, USA.
Georgios GlynatsisDepartment of Physics, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL, 32610, USA.
Dietmar W SiemannDivision of Hematology/Oncology, UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA.
Jonathan D LichtDivision of Hematology/Oncology, UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA.
Chenglong LiDepartment of Medicinal Chemistry, University of Florida, Gainesville, FL, 32610, USA.
Frederic J KayeDivision of Hematology/Oncology, UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA.
Mingyi XieUF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA.
Youhua TanThe Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518000, China; Research Institute of Smart Ageing, The Hong Kong Polytechnic University, 999077, Hong Kong, China; Department of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, China.
Lizi WuUF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, 32610, USA.
Trever G BivonaDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA; Chan-Zuckerberg Biohub Network, San Francisco, CA, 94158, USA. Electronic address: trever.bivona@ucsf.edu.
Juan GuanCollege of Pharmacy, Division of Chemical Biology and Medicinal Chemistry, University of Texas at Austin, Austin, TX, 78712, USA. Electronic address: juanguan@utexas.edu.
Xin TangDepartment of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32610, USA; UF Health Cancer Center, University of Florida, Gainesville, FL, 32610, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, 32610, USA. Electronic address: xin.tang@ufl.edu.

Funding

UCSF Project 1U54CA224081 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trever G Bivona · 2017 to 2026
$12.9M
The Cancer Target Discovery and Development Network at UCSFU01CA217882 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BANDYOPADHYAY, SOURAV, BIVONA, TREVER G · 2017 to 2021
$5.2M
RNA metabolism mediated by the Integrator complexR35GM128753 · NIGMS · UNIVERSITY OF FLORIDA · PI MINGYI XIE · 2018 to 2026
$4.0M
Characterization of YAP as a rational companion target in lung cancerR01CA204302 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trever G Bivona · 2017 to 2026
$3.7M
Rational Combined Inhibition of NF-kB and EGFR to Optimize Lung Cancer TreatmentR01CA169338 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2013 to 2023
$3.4M
Signaling and Targeting of CRTC1-MAML2 Fusion Oncoprotein in Salivary Gland TumorR01DE023641 · NIDCR · UNIVERSITY OF FLORIDA · PI Lizi Wu · 2014 to 2026
$3.3M
Nuclear Dysfunction in Cancer: The Role of Mechanical Stresses Transmittedby the LINC ComplexU01CA225566 · NCI · UNIVERSITY OF FLORIDA · PI LELE, TANMAY P. · 2020 to 2024
$3.1M
(PQ7) Defining a new mode of RAS signaling in cancer from cytoplasmic protein granulesR01CA231300 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G, HUANG, BO · 2019 to 2023
$2.3M
Mechanisms of Assembly and Functional Regulation in Non-canonical Biomolecular CondensatesR35GM146877 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI Juan Guan · 2022 to 2026
$2.0M
Optimizing biologically-based rational polytherapy in ALK+ lung cancerR01CA211052 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2017 to 2021
$1.8M
Aberrant CRTC activation as a unique vulnerability of lung cancer with LKB1 inactivationR01CA234351 · NCI · UNIVERSITY OF FLORIDA · PI WU, LIZI · 2019 to 2023
$1.7M
Mechanisms and Functions of Unconventional Intercellular Calcium Waves in Electrically Non-excitable CellsR35GM150812 · NIGMS · UNIVERSITY OF FLORIDA · PI Xin Tang · 2023 to 2026
$1.4M
NCI NIH HHS R01 CA169338NCI NIH HHS R01 CA204302NCI NIH HHS R01 CA211052NCI NIH HHS R01 CA231300NCI NIH HHS R01 CA234351NCI NIH HHS T32 CA257923NCI NIH HHS U01 CA217882NCI NIH HHS U01 CA225566NCI NIH HHS U54 CA224081NIDCR NIH HHS R01 DE023641NIGMS NIH HHS R35 GM128753NIGMS NIH HHS R35 GM146877NIGMS NIH HHS R35 GM150812
6 · The paper itself

Abstract

Drug resistance is a leading cause of cancer treatment failure and tumor recurrence. Identifying new methods that eliminate life-threatening drug-resistant cancer cells (DRCs) can enhance tumor cell eradication and improve patient outcomes. Here we report that human non-small cell lung cancer (NSCLC) DRCs show previously unrecognized increased sensitivity to mechanical stimuli compared to drug-susceptible lung cancer cells (DSCs) in vitro. Exploiting this heightened mechanical sensitivity, the combination of physiologically soft culture microenvironment with targeted therapies reduces the survival of DRCs through regulating yes-associated-protein (YAP) translocation between nucleus and cytoplasm. Our clinical studies confirm that DRCs possess heightened YAP nuclear localization in both NSCLC patient-derived organoid models and patient tissues, indicating high potential of eradicating DRCs by mechanical stimuli in vivo. Further, our mechanistic analyses, including quantitative imaging, transcriptomic profiling, and pharmacological evaluations reveal that the alterations in nuclear force sensing, rather than actomyosin contractility or Hippo-YAP pathway activation in DRCs, primarily drive the heightened YAP mechanosensitivity. This work highlights the crucial difference in mechanosensitivity between DRCs and DSCs, and points to mechanobiological targeting of these cells as a novel strategy to overcome drug resistance and enhance cancer therapy.

Indexed as

Adaptor Proteins, Signal TransducingCarcinoma, Non-Small-Cell LungCell NucleusDrug Resistance, NeoplasmLung NeoplasmsMechanotransduction, CellularTranscription FactorsCell Line, TumorHumansYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingTranscription FactorsYAP1 protein, humanYAP-Signaling ProteinsCRISPR/Cas9-engineered endogenous protein labellingDrug resistanceDrug-resistant cancer cells (DRCs)Drug-tolerant persister cells (DTPs)MechanobiologyMechano-targeted cancer vulnerabilityNuclear mechanicsOptical interrogationYes-associated protein (YAP)

Identifiers

PMID41443038
PMCPMC13179723

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